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Inflammation Research
Published in: Inflammation Research 9/2011

01-09-2011 | Original Research Paper

Inhibition of inflammatory mediators and related signaling pathways by macrophage-stimulating protein in rheumatoid arthritis synovial fibroblasts

Authors: Xiang-min Tong, Jian-chao Wang, Yuedi shen, Jun-jun Xie, Jun-yu Zhang, Jie Jin

Published in: Inflammation Research | Issue 9/2011

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Abstract

Objective

To evaluate the mechanism of macrophage-stimulating protein (MSP)-mediated inhibition of inflammatory cytokine and chemokine production in rheumatoid arthritis synovial fibroblasts (RASF).

Materials and methods

RASF were treated with different concentrations (0, 0.5, 1, 5 and 10 ng/ml) of MSP with or without 1 μg/mL lipopolysaccharide (LPS). The protein expressions of IL-1β, TNF-α, IL-18, MIP-1, MCP-1, RANTES and PGE2 were analyzed by enzyme-linked immunosorbent assays (ELISA). The total nitric oxide (NO) concentration was determined using the Griess reaction. The protein expressions of iNOS, COX-2, NF-κB(p-p65), IKB-α, IKB-β, p-P38, p-Erk1/2 (P-P42/44) and p-AKT were detected by Western blotting.

Results

MSP markedly inhibited expression of inflammatory cytokines (IL-1β, TNF-α and IL-18), chemokines (MIP-1, MCP-1 and RANTES) and iNOS, NO, COX-2 and PGE2 in RASF stimulated by LPS. MSP treatment decreased expressions of p-IκBα, p-IKBβ and p-P65 in RASF in a concentration-dependent manner. Expressions of p-AKT, p-p38 and p-Erk1/2 were also inhibited markedly in RASF stimulated by LPS after treatment with MSP in a concentration-dependent manner.

Conclusion

MSP could inhibit the inflammatory cycle by suppressing inflammatory mediators and activation of NF-κB as well. The inhibitory effect of MSP on LPS-stimulated RASF may act through suppression of multiple signals such as the PI3K/AKT and/or MAPK pathways.
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Metadata
Title
Inhibition of inflammatory mediators and related signaling pathways by macrophage-stimulating protein in rheumatoid arthritis synovial fibroblasts
Authors
Xiang-min Tong
Jian-chao Wang
Yuedi shen
Jun-jun Xie
Jun-yu Zhang
Jie Jin
Publication date
01-09-2011
Publisher
SP Birkhäuser Verlag Basel
Published in
Inflammation Research / Issue 9/2011
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-011-0338-1

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